A. Field of the Invention
The present invention relates to a new and improved test device for the assay of fluids to determine the presence of a chemical compound, such as glucose; lower alcohols, such as ethanol; cholesterol; and uric acid and, particularly to a new and improved method and device for measuring glucose. More particularly, the present invention relates to a new and improved whole blood compatible, glucose test strip including a reactant system incorporated into a carrier matrix made from a silicon-containing polymerizable material permeable to glucose and to a new and improved method of quantitatively measuring glucose in whole blood.
B. Description of the Prior Art
Devices that measure fluctuations in a person's blood sugar, or glucose levels have become everyday necessities for many of the nation's seven million diabetics. Because this disorder can cause dangerous anomalies in blood chemistry and is believed to be a contributor to vision loss and kidney failure, most diabetics need to test themselves periodically and adjust their glucose count accordingly, usually with insulin injections. Patients who are insulin dependent--about 10% to 15% of diabetics--are instructed by doctors to check their blood-sugar levels as often as four times daily.
For years the solution for diabetics was one of several urinanalysis kits that, despite repeated improvements, provide imprecise measurements of glucose in the blood. Examples of early urine testing for glucose are described in U.S. Pat. Nos. 2,387,244 and 3,164,534. Later, reagent strips for urine testing were developed. Testing of urine for glucose, however, is limited in accuracy particularly since the renal threshhold for glucose spillage into the urine is different for each individual. Moreover, sugar (glucose) in urine is a sign that the glucose was too high several hours prior to the test because of the time delay in glucose reaching the urine. Readings taken from the urine, therefore, are indicative of the glucose level in the blood several hours before the urine is tested.
More accurate readings are possible by taking readings directly from blood to determine current glucose levels. The advent of home blood tests is considered by some to be the most significant advance in the care of diabetics since the discovery of insulin in 1921. Home blood glucose testing was made available with the development of reagent strips for whole blood testing. The reagent strip includes a reactant system comprising an enzyme, such as glucose oxidase, capable of catalyzing the oxidation reaction of glucose to gluconic acid and hydrogen peroxide; an indicator or oxidizable dye, such as o-tolidine; and a substance having peroxidative activity capable of catalyzing the oxidation of the indicator. The dye or indicator turns a visually different shade of color depending upon the extent of oxidation - dependent upon the concentration of glucose in the blood sample.
The reactions occurring in the reaction system are represented as follows: ##STR1## Extant reagent strips generally include a matrix material such as a bibulous, e.g., cellulosic, material impregnated with the reactant system capable of reacting with glucose as described above, and a matrix overcoating material capable of filtering out blood cells to prevent the blood cells from staining the matrix material. The overcoating material is necessary so that the colored blood cells do not interfere with proper determination of the dye color produced by dye oxidation. The colored blood cells can be wiped or washed off of the overcoating material before color analysis. The overcoating blood cell filter material was difficult to apply and it was difficult in manufacturing to provide a closely bonded, uniform coating. Examples of reagent strips of this type are described in U.S. Pat. Nos. 3,164,534 and 3,092,465. A breakthrough in self-care came in 1979, when the Ames Division of Miles Laboratories brought out its VISIDEX home blood testing kit. The VISIDEX home blood testing kit consists of disposable chemically coated plastic strips. When blood drawn by pricking a finger is placed on one of these strips, the resulting color change indicates the glucose content in the blood based on light reflection from the blood-contacted reagent strip.
The most significant advantages of the current technology available for home use reagent strips are low cost (roughly fifty cents per use) and a short, e.g. one minute, response time. There are significant problems with reagent strips, however. One of the most significant problems with extant reagent strips for whole blood glucose testing is that the strips are impregnated with an indeterminable amount and concentration of the reactant system. Further, the reactant system impregnated reagent strips cannot be manufactured having a completely homogeneous concentration of reactants, because of the incompletely homogeneous chemical uptake of the matrix, e.g., bibulous materials. Further, because of the imprecise nature of impregnation and differences in chemical uptake through the bibulous material volume, the concentration of reactants is imprecise, and varies throughout the strip volume. Further, blood wiped or washed from the surface of bibulous materials to obtain a more accurate visual indication of change resulting from glucose reaction, easily can change the surface of the bibulous material unless coated with a protective coating of material capable of filtering out hemoglobin or other coloring bodies found in whole blood making it much more difficult to make a color chart comparison and an accurate glucose concentration determination.
Silicone polymerized materials have not been used in the prior art as glucose-permeable matrix materials. Although prior art silicone rubbers are whole blood compatible and oxygen permeable, they are not glucose permeable -an essential function of a glucose reactant matrix material. An example of an electrode membrane assembly with a silicone rubber secondary membrane is disclosed in U.S. Pat. No. 3,979,274, but such material is not glucosepermeable.
In addition to whole blood, there are other body fluids from which glucose can be measured. Published data indicate that sweat is an ultrafiltrate of blood with a low, variable glucose concentration. The literature indicates that glucose concentration in the interstitial extracellular space and intramuscular or subcutaneous locations is lower than blood glucose but this is believed to be a good measure of the blood glucose. Thus, glucose reaches the underside of the skin in potentially useful amounts.
Conventional sensors for measuring glucose in sweat require withdrawing a sample or employing elaborate procedures or testing equipment. Examples of conventional sensors are disclosed in U.S. Pat. Nos. 4,044,772; 4,195,641; and 4,329,999. There is a need for a noninvasive sensor for measuring glucose in a body fluid such as sweat. The preferred sensor would not include elaborate equipment or require elaborate procedures. In accordance with the present invention, the reagent strips disclosed herein are sufficiently glucose permeable and produce a detectable color change upon contact with body sweat.